CONICET | Buscador de Institutos y Recursos Humanos

Pancreatic ductal adenocarcinoma (PDAC) represents a very aggressive type of pancreatic cancer worldwide. PDX1 is an important transcription factor both for embryonic development of the pancreas and for differentiation of progenitor cells into Langerhans islet beta cells. Although its overexpression has been reported in many types of cancer, including pancreatic cancer, its role as a pro or anti-tumor factor is contradictory. Therefore, our aim was to analyze the effect of the overexpression of PDX1 of PDAC cells on tumor aggressiveness. To induce PDX1, PANC-1 cells were treated with BRD7552 for 9 days. Overexpression of PDX1 was confirmed by Western Blot analysis and no cytotoxic effect was observed by MTT nor Trypan Blue assay on treated cells. Wound healing assay showed a significant reduction in migration rate compared to control. Preliminary results obtained by flow cytometry assay revealed an increased in G1 phase in treated cells compare to control. Cell confluency assay showed a significant decreased in the occupied area of treated cells compare to control. However, analysis of Ki67 and Fosfo-H3 immunostaining exhibited no significant difference in cell proliferation rates. Treated PANC-1 cells were implanted onto the chorioallantoic membrane of chick embryos and tumor growth was measured at different stages observing a decreased tumor size between day 7th and 8th post-implantation compared to control. Hematoxilyn-eosyn staining revealed a decrease in tumor invasion onto the chorioallantoic membrane in treated cells compared to control. Among tumors, different phenotypes were observed according to morphology, coloration and presence of invasive blood vessels in the tumor between treated cells and control. In conclusion, overexpression of PDX1 in PANC-1 cells affects cell cycle, reduce the occupied area and inhibits their migratory potential in vitro and tumor growth in ovo.

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